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https://www.readbyqxmd.com/read/29161316/acute-exercise-alters-skeletal-muscle-mitochondrial-respiration-and-h2o2-emission-in-response-to-hyperinsulinemic-euglycemic-clamp-in-middle-aged-obese-men
#1
Adam J Trewin, Itamar Levinger, Lewan Parker, Christopher S Shaw, Fabio R Serpiello, Mitchell J Anderson, Glenn K McConell, David L Hare, Nigel K Stepto
Obesity, sedentary lifestyle and aging are associated with mitochondrial dysfunction and impaired insulin sensitivity. Acute exercise increases insulin sensitivity in skeletal muscle; however, whether mitochondria are involved in these processes remains unclear. The aim of this study was to investigate the effects of insulin stimulation at rest and after acute exercise on skeletal muscle mitochondrial respiratory function (JO2) and hydrogen peroxide emission (JH2O2), and the associations with insulin sensitivity in obese, sedentary men...
2017: PloS One
https://www.readbyqxmd.com/read/29161229/sex-and-dose-specific-effects-of-maternal-bisphenol-a-exposure-on-pancreatic-islets-of-first-and-second-generation-adult-mice-offspring
#2
Amita Bansal, Cetewayo Rashid, Frances Xin, Changhong Li, Erzsebet Polyak, Anna Duemler, Tom van der Meer, Martha Stefaniak, Sana Wajid, Nicolai Doliba, Marisa S Bartolomei, Rebecca A Simmons
BACKGROUND: Exposure to the environmental endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with the increased risk of diabetes and obesity. However, the underlying mechanisms remain unknown. We recently demonstrated that perinatal BPA exposure is associated with higher body fat, impaired glucose tolerance, and reduced insulin secretion in first- (F1) and second-generation (F2) C57BL/6J male mice offspring. OBJECTIVE: We sought to determine the multigenerational effects of maternal bisphenol A exposure on mouse pancreatic islets...
September 27, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29161091/dealing-with-stress-defective-metabolic-adaptation-in-chronic-obstructive-pulmonary-disease-pathogenesis
#3
Charalambos Michaeloudes, Pankaj K Bhavsar, Sharon Mumby, Kian Fan Chung, Ian M Adcock
The mitochondrion is the main site of energy production and a hub of key signaling pathways. It is also central in stress-adaptive response due to its dynamic morphology and ability to interact with other organelles. In response to stress, mitochondria fuse into networks to increase bioenergetic efficiency and protect against oxidative damage. Mitochondrial damage triggers segregation of damaged mitochondria from the mitochondrial network through fission and their proteolytic degradation by mitophagy. Post-translational modifications of the mitochondrial proteome and nuclear cross-talk lead to reprogramming of metabolic gene expression to maintain energy production and redox balance...
November 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29161084/mitochondrial-dysfunction-linking-obesity-and-asthma
#4
Naveen K Bhatraju, Anurag Agrawal
The bidirectional epidemiological association between asthma and obesity is well known. Recent evidence suggests that there is an intersection of the pathophysiological molecular pathways leading to either obesity or asthma, at the level of mitochondria. This is not surprising, because mitochondria, beyond their roles as the metabolic powerhouses of the cell, serve as sensors of threats, regulators of stress signaling, and effectors of cytotoxicity. Reduced mitochondrial function and low metabolic activity are well-recognized features of obesity...
November 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29161077/mitochondrial-dysfunction-in-pulmonary-fibrosis
#5
Sunad Rangarajan, Karen Bernard, Victor J Thannickal
The aging of the human population has resulted in an unprecedented increase in the incidence and prevalence of age-related diseases, including those of the lung. Idiopathic pulmonary fibrosis is a disease of aging, and is characterized by a progressive decline in lung function and high mortality. Recent studies suggest that mitochondrial dysfunction, which can accompany aging phenotypes, may contribute to the pathogenesis of idiopathic pulmonary fibrosis. In this review, we explore current evidence for mitochondrial dysfunction in alveolar epithelial cells, fibroblasts, and immune cells that participate in the fibrotic process...
November 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29160855/effects-of-red-palm-oil-on-myocardial-antioxidant-enzymes-nitric-oxide-synthase-and-heart-function-in-spontaneously-hypertensive-rats
#6
Emma Katengua-Thamahane, Barbara Szeiffova Bacova, Iveta Bernatova, Matus Sykora, Vladimir Knezl, Jacques Van Rooyen, Narcis Tribulova
The purpose of this study was to investigate the effect of antioxidants rich red palm oil (RPO) supplementation on cardiac oxidative stress known as crucial factor deteriorating heart function in hypertension. 3-month-old, male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were fed standard rat chow without or with RPO (0.2 mL/day/5 weeks). General characteristic of rats were registered. Left ventricular tissue (LV) was used to determine expression of superoxide dismutases (SOD1, SOD2) and glutathione peroxidases (Gpx) as well as activity of nitric oxide synthase (NOS)...
November 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29160846/a-triphenylphosphonium-functionalized-mitochondriotropic-nanocarrier-for-efficient-co-delivery-of-doxorubicin-and-chloroquine-and-enhanced-antineoplastic-activity
#7
Katerina N Panagiotaki, Zili Sideratou, Spiros A Vlahopoulos, Maria Paravatou-Petsotas, Michael Zachariadis, Nikolas Khoury, Vassilis Zoumpourlis, Dimitris Tsiourvas
Drug delivery systems that target subcellular organelles and, in particular, mitochondria are considered to have great potential in treating disorders that are associated with mitochondrial dysfunction, including cancer or neurodegenerative diseases. To this end, a novel hyperbranched mitochondriotropic nanocarrier was developed for the efficient co-delivery of two different (both in chemical and pharmacological terms) bioactive compounds. The carrier is based on hyperbranched poly(ethyleneimine) functionalized with triphenylphosphonium groups that forms ~100 nm diameter nanoparticles in aqueous media and can encapsulate doxorubicin (DOX), a well-known anti-cancer drug, and chloroquine (CQ), a known chemosensitizer with arising potential in anticancer medication...
November 21, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29160844/altered-aconitase-2-activity-in-huntington-s-disease-peripheral-blood-cells-and-mouse-model-striatum
#8
Chiung-Mei Chen, Yih-Ru Wu, Kuo-Hsuan Chang
Huntington's disease (HD) is caused by an unstable cytosine adenine guanine (CAG) trinucleotide repeat expansion encoding a polyglutamine tract in the huntingtin protein. Previously, we identified several up- and down-regulated protein molecules in the striatum of the Hdh((CAG)150) knock-in mice at 16 months of age, a mouse model which is modeling the early human HD stage. Among those molecules, aconitase 2 (Aco2) located in the mitochondrial matrix is involved in the energy generation and susceptible to increased oxidative stress that would lead to inactivation of Aco2 activity...
November 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29160745/the-unveiling-of-the-warburg-effect-and-the-inscribed-innovative-approach-to-a-radical-non-toxic-anticancer-therapy
#9
Olivia Crociani, Ilaria Marzi, Maria Grazia Cipolleschi, Antonella Mannini, Massimo Contini, Massimo Olivotto
The purpose of this research has been deciphering the Warburg paradox, the biochemical enigma unsolved since 1923. This paradox consists of the aerobic pyruvate conversion to lactate brought about by anaplastic cancer, through the metabolic pathway known as aerobic glycolysis. This pathway implies a heavy energetic waste. We solved the enigma by demonstrating that its specific character, i.e. the forced aerobic lactate exportation, represents a crucial metabolic device to counteract the cytotoxic effect produced by an excess of pyruvate at the connection of glycolysis with the Krebs cycle...
November 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29160414/predicting-pathway-cross-talks-in-ankylosing-spondylitis-through-investigating-the-interactions-among-pathways
#10
Xiang Gu, Cong-Jian Liu, Jian-Jie Wei
Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted...
November 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29159800/effects-of-combined-helium-pre-post-conditioning-on-the-brain-and-heart-in-a-rat-resuscitation-model
#11
C Aehling, N C Weber, C J Zuurbier, B Preckel, R Galmbacher, K Stefan, M W Hollmann, E Popp, J Knapp
BACKGROUND: The noble gas helium induces cardio- and neuroprotection by pre- and post-conditioning. We investigated the effects of helium pre- and post-conditioning on the brain and heart in a rat resuscitation model. METHODS: After approval by the Animal Care Committee, 96 Wistar rats underwent cardiac arrest for 6 min induced by ventricular fibrillation. Animals received 70% helium and 30% oxygen for 5 min before cardiac arrest and for 30 min after restoration of spontaneous circulation (ROSC)...
November 20, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/29159707/propionyl-coa-carboxylase-pcca-1-and-pccb-1-gene-deletions-in-caenorhabditis-elegans-globally-impair-mitochondrial-energy-metabolism
#12
Kimberly A Chapman, Julian Ostrovsky, Meera Rao, Stephen D Dingley, Erzsebet Polyak, Marc Yudkoff, Rui Xiao, Michael J Bennett, Marni J Falk
Propionic acidemia (PA) is a classical inborn error of metabolism with high morbidity that results from the inability of the propionyl-CoA carboxylase (PCC) enzyme to convert propionyl-CoA to methylmalonyl-CoA. PA is inherited in an autosomal recessive fashion due to functional loss of both alleles of either PCCA or PCCB. These genes are highly conserved across evolutionarily diverse species and share extensive similarity with pcca-1 and pccb-1 in the nematode, Caenorhabditis elegans. Here, we report the global metabolic effects of deletion in a single PCC gene, either pcca-1 or pccb-1, in C...
November 20, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29159461/severe-hyperammonemic-encephalopathy-requiring-dialysis-aggravated-by-prolonged-fasting-and-intermittent-high-fat-load-in-a-ramadan-fasting-month-in-a-patient-with-cptii-homozygous-mutation
#13
P Phowthongkum, C Ittiwut, V Shotelersuk
BACKGROUND: Carnitine palmitoyltransferase II (CPTII) deficiency is a mitochondrial fatty acid oxidation disorder that can present antenatally as congenital brain malformations, or postnatally with lethal neonatal, severe infantile, or the most common adult myopathic forms. No case of severe hyperammonemia without liver dysfunction has been reported. CASE PRESENTATION: We described a 23-year-old man who presented to the emergency department with seizures and was found to have markedly elevation of serum ammonia...
November 21, 2017: JIMD Reports
https://www.readbyqxmd.com/read/29159021/mitochondrial-uncoupler-triclosan-induces-vasorelaxation-of-rat-arteries
#14
Xiyue Zhang, Xinzi Zhang, Yanqiu Zhang, Mingyu Liu, Jing Jin, Jie Yan, Xin Shen, Nan Hu, Deli Dong
Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca(2+)]i, mitochondrial reactive oxygen species (mitoROS), and mitochondrial membrane potential of smooth muscle cells (A10 cells) were measured using laser scanning confocal microscopy...
November 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29158819/pro-inflammatory-cxcr3-impairs-mitochondrial-function-in-experimental-non-alcoholic-steatohepatitis
#15
Jinghua Du, Xiang Zhang, Juqiang Han, Kwan Man, Yanquan Zhang, Eagle Sh Chu, Yuemin Nan, Jun Yu
Mitochondrial dysfunction plays a crucial role in the development of non-alcoholic steatohepatitis (NASH). However, the regulator of mitochondrial dysfunction in the pathogenesis of NASH is still largely unclear. CXCR3 is an essential pro-inflammatory factor in chronic liver diseases. We explored the significance of CXCR3 in regulating mitochondrial function during NASH development in animal models and cultured hepatocytes. METHODS: The effects of CXCR3 on mitochondrial function were evaluated by genetic knockout or pharmacological inhibition in mouse models and in vitro...
2017: Theranostics
https://www.readbyqxmd.com/read/29158541/dysregulation-of-mitochondrial-function-and-biogenesis-modulators-in-adipose-tissue-of-obese-children
#16
R Zamora-Mendoza, H Rosas-Vargas, M T Ramos-Cervantes, P Garcia-Zuniga, H Perez-Lorenzana, P Mendoza-Lorenzo, A Perez-Ortiz, J Estrada, A Miliar-Garcia, E Lara-Padilla, G Ceballos, A Rodriguez, F Villarreal, I Ramirez-Sanchez
BACKGROUND/OBJECTIVES: We aimed to evaluate mitochondrial biogenesis (MB), structure, metabolism, and dysfunction in abdominal adipose tissue from male pediatric patients with obesity. SUBJECTS/METHODS: Samples were collected from five children with obesity (percentile ⩾95) and five eutrophic boys (percentile ⩾5/⩽85) (8-12 years old) following parental informed consent. We analyzed the expression of key genes involved in MB (SIRT1, PPARγ, PGC1α, NRF1, NRF2, and TFAM) and surrogates for mitochondrial function/structure/metabolism (porin, TOMM20, complex I and V, UCP1, UCP2, SIRT3, SOD2) by Western blot...
November 21, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29158468/evaluating-the-mechanism-and-therapeutic-potential-of-ptc-028-a-novel-inhibitor-of-bmi-1-function-in-ovarian-cancer
#17
Anindya Dey, Xunhao Xiong, Aleia Crim, Shailendra Kumar Dhar Dwivedi, Soumyajit Banerjee Mustafi, Priyabrata Mukherjee, Liangxian Cao, Nadiya Sydorenko, Ramil Baiazitov, Young-Choon Moon, Melissa Dumble, Thomas Davis, Resham Bhattacharya
BMI-1, also known as a stem cell factor, is frequently upregulated in several malignancies. Elevated expression of BMI-1 correlates with poor prognosis and is therefore considered a viable therapeutic target in a number of malignancies including ovarian cancer. Realizing the immense pathological significance of BMI-1, small molecule inhibitors against BMI1 are recently being developed. In the current study, we functionally characterize PTC-028, an orally bioavailable compound that decreases BMI-1 levels by post-translational modification We report that PTC-028 treatment selectively inhibits cancer cells in clonal growth and viability assays whereas normal cells remain unaffected...
November 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29158418/a-novel-pkhd1-mutation-interacts-with-the-nonobese-1diabetic-genetic-background-to-cause-autoimmune-cholangitis
#18
Wenting Huang, Daniel B Rainbow, Yuehong Wu, David Adams, Pranavkumar Shivakumar, Leah Kottyan, Rebekah Karns, Bruce Aronow, Jorge Bezerra, M Eric Gershwin, Laurence B Peterson, Linda S Wicker, William M Ridgway
We previously reported that NOD.c3c4 mice develop spontaneous autoimmune biliary disease (ABD) with anti-mitochondrial Abs, histopathological lesions, and autoimmune T lymphocytes similar to human primary biliary cholangitis. In this article, we demonstrate that ABD in NOD.c3c4 and related NOD ABD strains is caused by a chromosome 1 region that includes a novel mutation in polycystic kidney and hepatic disease 1 (Pkhd1). We show that a long terminal repeat element inserted into intron 35 exposes an alternative polyadenylation site, resulting in a truncated Pkhd1 transcript...
November 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29158324/control-of-rab7-activity-and-localization-through-the-retromer-tbc1d5-complex-enables-rab7-dependent-mitophagy
#19
Ana Jimenez-Orgaz, Arunas Kvainickas, Heike Nägele, Justin Denner, Stefan Eimer, Jörn Dengjel, Florian Steinberg
Retromer is an endosomal multi-protein complex that organizes the endocytic recycling of a vast range of integral membrane proteins. Here, we establish an additional retromer function in controlling the activity and localization of the late endosomal small GTPase RAB7. Surprisingly, we found that RAB7 not only decorates late endosomes or lysosomes, but is also present on the endoplasmic reticulum, trans-Golgi network, and mitochondrial membranes, a localization that is maintained by retromer and the retromer-associated RAB7-specific GAP TBC1D5...
November 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29158290/a-comparative-proteome-profile-of-female-mouse-gonads-suggests-a-tight-link-between-the-electron-transport-chain-and-meiosis-initiation
#20
Cong Shen, Mingrui Li, Pan Zhang, Yueshuai Guo, Hao Zhang, Bo Zheng, Hui Teng, Tao Zhou, Xuejiang Guo, Ran Huo
Generation of haploid gametes by meiosis is a unique property of germ cells and is critical for sexual reproduction. Leaving mitosis and entering meiosis is a key step in germ cell development. Several inducers or intrinsic genes are known to be important for meiotic initiation, but the regulation of meiotic initiation, especially at the protein level, is still not well understood. We constructed a comparative proteome profile of female mouse fetal gonads at specific time points (11.5, 12.5, and 13.5 days post coitum), spanning a critical window for initiation of meiosis in female germ cells...
November 20, 2017: Molecular & Cellular Proteomics: MCP
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